Calcium-Overload-Mediated Tumor Therapy by Calcium Peroxide Nanoparticles

Calcium overload, characterized by an abnormal cytoplasm accumulation of free calcium ions (Ca²⁺), is a widely recognized cause of damage in numerous cell types and even of cell death. This undesirable destructive process can become a new tool applicable to cancer treatment. Herein, on the basis of the unique biological effect of Ca²⁺, we demonstrate a highly efficient strategy for tumor therapy by utilizing pH-sensitive sodium-hyaluronate-modified calcium peroxide nanoparticles (SH-CaO₂ NPs). These NPs create an artificial calcium overloading stress in tumor cells, which is responsible for cell death. Notably, the killing effect is not limited to tumor types or hypoxic cells, and normal cells are more tolerant of the adverse influence of NPs than tumor cells. The Ca²⁺ enrichment also increases the likelihood of tumor calcification, which could contribute to in vivo tumor inhibition and facilitate medical imaging to monitor the treatment efficacy.